A longitudinal fixel-based analysis of white matter alterations in patients with Parkinson's disease

Introduction: Disruption to white matter pathways is an important contributor to the pathogenesis of Parkinson's disease. Fixel-based analysis has recently emerged as a useful fiber-specific tool for examining white matter structure. In this longitudinal study, we used Fixel-based analysis to investigate white matter changes occurring over time in patients with Parkinson's disease. Methods: Fifty patients with idiopathic Parkinson's disease (27 men and 23 women; mean age: 61.8 +/- 6.1 years), were enrolled. Diffusion-weighted imaging and clinical examinations were performed at three different time points (baseline, first follow-up [after a mean of 24 +/- 2 months], and second follow-up [after a mean of 40 +/- 3 months]). Additional 76 healthy control subjects (38 men and 38 women; mean age: 62.3 +/- 5.5 years) were examined at baseline. The following fixel-based metrics were obtained: fiber density (FD), fiber bundle cross-section (FC), and a combined measure of both (FDC). Paired comparisons of metrics between three different time points were performed in patients. Linear regression was implemented between longitudinal changes of fixel-based metrics and the corresponding modifications in clinical parameters. A family-wise error corrected p < 0.05 was considered statistically significant. Results and Discussions: Early degeneration in the splenium of corpus callosum was identified as a typical alteration of Parkinson's disease over time. At follow-up, we observed significant FDC reductions compared with baseline in white matter, noticeably in corpus callosum; tapetum; cingulum, posterior thalamic radiation, corona radiata, and sagittal stratum. We also identified significant FC decreases that reflected damage to white matter structures involved in Parkinson's disease -related pathways. Fixel-based metrics were found to relate with a deterioration of 39-item Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale and activity of daily living. A Parkinson's disease -facilitated aging effect was observed in terms of white matter disruption. Conclusion: This study provides a thorough fixel-based profile of longitudinal white matter alterations occurring in patients with Parkinson's disease and new evidence of FC as an important role in white matter degeneration in this setting.